In:
Journal of Innate Immunity, S. Karger AG, Vol. 4, No. 3 ( 2012), p. 301-311
Abstract:
〈 i 〉 Staphylococcus aureus 〈 /i 〉 is a leading human pathogen that causes a large variety of diseases. In vitro studies have shown that 〈 i 〉 S. aureus 〈 /i 〉 secretes several small proteins that block specific elements of the host innate immune system, but their role in bacterial pathogenicity is unknown. For instance, the extracellular complement-binding protein (Ecb) impairs complement activation by binding to the C3d domain of C3. Its homolog, the extracellular fibrinogen-binding protein (Efb), is known to block both complement activation and neutrophil adhesion to fibrinogen. Here, we show that targeted inactivation of the genes encoding Ecb and Efb strongly attenuates 〈 i 〉 S. aureus 〈 /i 〉 virulence in a murine infection model: mice experienced significantly higher mortality rates upon intravenous infection with wild-type bacteria (79%) than with an isogenic ΔEcbΔEfb mutant (21%). In addition, Ecb and Efb are both required for staphylococcal persistence in host tissues and abscess formation in the kidneys (27% for wild-type vs. 7% for the ΔEcbΔEfb mutant). During staphylococcal pneumonia, Ecb and Efb together promote bacterial survival in the lungs (p = 0.03) and block neutrophil influx into the lungs. Thus, Ecb and Efb are essential to 〈 i 〉 S. aureus 〈 /i 〉 virulence in vivo and could be attractive targets in future vaccine development efforts.
Type of Medium:
Online Resource
ISSN:
1662-811X
,
1662-8128
Language:
English
Publisher:
S. Karger AG
Publication Date:
2012
detail.hit.zdb_id:
2455818-7
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